Submissions for variant NM_000368.5(TSC1):c.1163T>C (p.Leu388Pro)

gnomAD frequency: 0.00041  dbSNP: rs377598226

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000734481	SCV000514993	likely benign	not provided	2021-02-23	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26226092)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083120	SCV000552299	benign	Tuberous sclerosis 1	2024-01-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000567359	SCV000675368	likely benign	Hereditary cancer-predisposing syndrome	2021-09-30	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Eurofins Ntd Llc (ga)	RCV000734481	SCV000862627	uncertain significance	not provided	2018-08-22	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001083120	SCV002040123	likely benign	Tuberous sclerosis 1	2021-11-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000567359	SCV002530879	likely benign	Hereditary cancer-predisposing syndrome	2021-02-17	criteria provided, single submitter	curation
Revvity Omics, Revvity	RCV000734481	SCV004236972	uncertain significance	not provided	2023-05-22	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003995989	SCV004840479	uncertain significance	Tuberous sclerosis syndrome	2024-02-05	criteria provided, single submitter	clinical testing	This missense variant replaces leucine with proline at codon 388 of the TSC1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with tuberous sclerosis complex in the literature. This variant has been identified in 20/281880 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Myriad Genetics, Inc.	RCV001083120	SCV005404692	likely benign	Tuberous sclerosis 1	2024-08-09	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.
PreventionGenetics, part of Exact Sciences	RCV003902488	SCV004724564	likely benign	TSC1-related disorder	2023-07-17	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).